Leading the way to a cure

Lupus Research Update: 2012 Volume 3

Volume 3, 2012 - Online Edition | In This Issue

Looking at T Cell Function to Better Understand Lupus >
Back to Basics — T Cells... B Cells... And Lupus >
Researching B Cells Reveals Clues About Lupus >
Faces of Lupus: Sisterly Love in Michigan Benefits Everyone with Lupus >
Genetic Gateways to Understanding Lupus - New ALR Grant Awardees >
Lupus News Corner >

Researching B Cells Reveals Clues About Lupus

To fully grasp an understanding of lupus, leading scientists across the globe are looking to the immune system for answers — particularly the role that B cells play. Autoimmune disease expert, Dr. Peter K. Gregersen, is one such scientist.

During the ALR’s first critical years, he was a key advisor to SLEGEN, the organization’s genetics consortium, which went on to discover genes responsible for increasing the chances of developing lupus. Today, Dr. Gregersen’s own pioneering work on the genetic control of B cells has received funding through the ALR.

Dr. Gregersen, working with his scientific collaborator Dr. Betty Diamond, has identified an intronic polymorphism, or variation, in the gene CSK that is associated with risk of lupus — and the goal of their work is to study the effects of this variant on CSK expression, B-cell biology, and the cellular events and mechanisms in the development of the disease.

Introns are pieces of DNA that interrupt the coding region, and until recently, the function of these genes has remained obscure.

But in recent years, research has revealed new insights. Dr. Gregersen explains: “What has emerged is that many of these intronic regions of genes contain sequences, which regulate when the gene is turned on or off. This is, in fact, what we have found with CSK.”

By focusing on gene sequencing, Dr. Gregersen has found that this variant controls the amount of CSK produced. The CSK does not change; it’s just the amount that varies in certain B cells.

Dr. Gregersen clarifies: “In their immature state, B cells are associated with a lot of auto-reactive potential. And what is striking about our analyses of CSK is that it is most highly expressed in these very early B cell subsets. We believe that in lupus there is more CSK in these early B cells and that they have the potential to be auto-reactive.”

In deepening the basic understanding of lupus at the molecular level, Dr. Gregersen hopes that his work will lead to a new array of treatments for lupus patients.

When speaking about the ALR, he is quick to acknowledge its seminal role. “The ALR puts invaluable support behind creative ideas and excellent scientists. I have no doubt that it will continue to break new ground. And that means, when you can understand lupus, you immediately have a potential window into therapy.”

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